The goal is to develop improved diagnostic imaging agents for human melanoma based on a radiolabeled monoclonal antibody. P97 is an oncofetal antigen present on human melanoma tumor cells. Studies in nude mice have shown there is active concentration of anti-p97 antibody and Fab fragments directed against p97 antigen of human melanoma. The uptake is antigen specific, as documented by comparisons with radiolabeled control immunoglobulin and immune fragments. Ten patients have been studied with whole anti-p97 antibody, and uptake has been documented in metastatic lesions. About 88% of documented metastatic lesions have been imaged, and antigen-specific uptake in tumor has been documented by comparison to radiolabeled control immunoglobulin. Maximum target-to-nontarget ratios observed from human tumors, biopsied at 72 hours after intravenous administration of the anti-p97 antibody, are 7 to 1. Thirty-three patients with advanced malignant melanoma were studied on 47 occasions with I-131-labeled Fab (anti-p97). In 20 of these, a simultaneous administration of an I-125 labeled nonspecific Fab was performed. Antigen-specific localization was observed with average ratios of specific:nonspecific uptake of 3.7 (48 hours) and 3.4 (72 hours); uptake was correlated with tumor p97 concentrations. Twenty patients had positive scans. Antibody injections were well tolerated with the exception of four reactions: one episode of transient chills and fever; flushing and hypotension; and two skin rashes. All these reactions responded promptly to symptomatic therapy. Human antimouse antibodies were documented in the two patients who developed skin rashes.